ArticleClinical and translational medicine2026
Multiomics analyses revealed the roles of the epithelial-mesenchymal transition and novel early candidate diagnostic biomarkers in neonatal necrotising enterocolitis.
Article in Clinical and translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundNecrotizing enterocolitis (NEC) is a severe neonatal gastrointestinal disease with incompletely understood pathogenesis and a lack of reliable early biomarkers. We investigated intestinal molecular alterations associated with NEC and explored candidate diagnostic biomarkers.
methodsBulk proteomics of formalin-fixed paraffin-embedded intestinal tissues was integrated with spatial proteomics of an index NEC case, single-cell RNA sequencing, immunohistochemical validation, serum enzyme-linked immunosorbent assays, and a murine NEC model with pharmacological inhibition of Snail-mediated epithelial-mesenchymal transition (EMT).
resultsMultiomics analyses indicated layer-associated epithelial injury, inflammatory activation, and EMT-like fibroblast/myofibroblast remodelling during NEC. Single-cell sequencing of six intestinal samples showed reduced epithelial-cell abundance with increased fibroblast and smooth-muscle-cell proportions in NEC. In the murine model, CYD19 treatment was associated with improved intestinal pathology, survival, inflammatory cytokine profiles, and barrier-related readouts. ANXA2, RPL13, RPL23A, and RPS28 were identified as tissue candidate biomarkers and validated by immunohistochemistry. Serum ANXA2 was higher in NEC than in available non-NEC controls (AUC, 0.944) and showed exploratory discrimination between medical NEC and highly suspected cow's-milk protein allergy; the adjusted AUC was 0.899.
conclusionsNEC is associated with inflammation-linked EMT-like intestinal remodelling and epithelial injury. ANXA2 and selected ribosomal proteins are candidate tissue biomarkers, while serum ANXA2 warrants prospective multicentre validation as a blood-based diagnostic and risk-stratification biomarker. KEY POINTS: NEC was associated with epithelial injury, excessive inflammation, and EMT-like fibroblast/myofibroblast remodelling, as revealed by integrated bulk proteomics, spatial proteomics, and single-cell sequencing. Pharmacological inhibition of Snail-mediated EMT in a murine NEC model was associated with improved intestinal injury, inflammatory responses, barrier-related readouts, and survival. ANXA2, RPL13, RPL23A, and RPS28 were identified as candidate tissue biomarkers, while serum ANXA2 showed exploratory potential for NEC diagnosis and risk stratification.
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